New discovery from the team at Case Western Reserve University Hospital and University could lead to therapies for metabolic disease.

Metabolic diseases, such as obesity and type 2 diabetes, are endemic in the United States and occur in about 30 percent of the population. Skeletal muscle plays an important role in controlling sugar levels in the body, which is important for the development of metabolic diseases such as diabetes.

In a recent study, published in the Journal of Clinical Investigation, University Hospital (UH) Cleveland Medical Center, and Case Western Reserve University School of Medicine, researchers found that skeletal muscle significantly affects how the body stores and metabolizes fat.

In the study, Mukesh K. Jain, MD, senior author, Academic Director at UH, and Ellery Sedgwick Jr. President & Distinguished Scientist, and his team set out to investigate the role of a gene called Kruppel-like factor 15 (KLF15) in skeletal muscle. The team used a mouse model with muscle-specific KLF15 deletion.

This genetic manipulation leads to a striking phenotype: obesity, dyslipidemia (high amounts of circulating fat), glucose intolerance, insulin resistance and a predisposition to the development of non-alcoholic fatty liver disease. (NAFLD). Further investigation revealed that KLF15 controls skeletal muscle fat uptake and utilization. Without KLF15, fat cannot effectively enter the muscles and instead is deposited in the liver and white adipose tissue.

Dr Jain, who is also Professor of Medicine and Associate Dean of University Hospitals at Case Western Reserve, and Scientific Director, Harrington Discovery Institute at UH, explains: “We knew from previous work. of our team that the role of KLF15 is crucial for muscle health, as levels are increased in humans after exercise.” “Experimentally, the loss of KLF15 in muscle led to decreased exercise capacity in rats. The fact that KLF15 is also important for metabolic health is really exciting as it provides a potential molecular link between exercise and overall health.”

Researchers have also shown that diets rich in short-chain fatty acids (SCFAs) can improve aspects of metabolic disease. High-fiber foods, such as fruits, vegetables, beans, and whole grains are rich in SCFAs. Rats on this diet showed reduced weight gain and improved homeostasis (regulating blood sugar). In addition, obese mice fed this same diet lost weight and improved insulin sensitivity, suggesting that a SCFA-rich diet may serve as a preventive and therapeutic approach. for metabolic disease.

“The propensity to develop obesity and NAFLD in the presence of caloric excess underscores the importance of skeletal muscle fat metabolism and muscular cross-talk,” said Liyan Fan, first author of the study. important in the development of these serious diseases,” said Liyan Fan, first author of the study. “This helps us understand the different agents that contribute to metabolic disease and, in turn, target effective therapies.”

Collectively, these findings identify skeletal muscle as an important regulator of fat metabolism and liver health, and that a diet rich in SCFAs could be an effective and easy complementary therapy option. approach to metabolic disease due to impaired fat processing.

The next steps in this study involved exploring the role of muscle KLF15 in different nutritional states (i.e., fasting and exercise), and investigating the therapeutic potential of targeting target muscle KLF15.

References:

Liyan Fan, David R. Sweet, Domenick A. Prosdocimo, Vinesh Vinayachandran, Ernest R. Chan, Rongli Zhang, Olga Ilkayeva, Yuan Lu, Komal S. Keerthy, Chloe E. Booth, Christopher B. Newgard, Mukesh K. Jain. Muscle Krüppel-like factor 15 Regulates lipid flux and systemic metabolic homeostasis. Journal of Clinical Investigation, 2021; 131 (4) DOI: 10.1172/JCI139496

Source: Muscle factor that controls fat metabolism identified

The article is translated and edited by ykhoa.org – please do not reup without permission!

Translated by: thangngan2509